negative regulation of proteasomal protein catabolic process

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of proteasomal protein catabolic process. [GOC:BHF, GOC:rl, GOC:TermGenie, PMID:21669198]

Negative regulation of proteasomal protein catabolic process involves a complex interplay of mechanisms aimed at controlling the degradation of proteins by the proteasome. The proteasome is a multi-subunit protein complex responsible for the breakdown of misfolded, damaged, or short-lived proteins. Here's a detailed description of the biological process:

1. **Ubiquitination:** The initial step involves tagging target proteins with ubiquitin molecules. Ubiquitin is a small protein that acts as a signal for proteasomal degradation. This process, known as ubiquitination, is carried out by a cascade of enzymes:
* **E1 (Ubiquitin-activating enzyme):** Activates ubiquitin by attaching it to itself.
* **E2 (Ubiquitin-conjugating enzyme):** Transfers activated ubiquitin to an E3 ligase.
* **E3 (Ubiquitin ligase):** Recognizes specific target proteins and attaches ubiquitin to them.
2. **Polyubiquitination:** Multiple ubiquitin molecules are linked together, forming a polyubiquitin chain on the target protein. The specific type of polyubiquitin chain (e.g., K48-linked) is crucial for proteasomal recognition.
3. **Proteasome Binding:** The polyubiquitinated protein is recognized and bound to the proteasome. The 19S regulatory particle of the proteasome recognizes the polyubiquitin chains and unfolds the target protein before it enters the 20S core particle.
4. **Protein Degradation:** The 20S core particle contains proteolytic active sites that break down the unfolded protein into short peptides.
5. **Deubiquitination:** The ubiquitin chains are removed from the degraded protein by deubiquitinating enzymes (DUBs). This step allows the recycling of ubiquitin molecules.

Negative regulation of proteasomal protein catabolic process involves mechanisms that inhibit or reduce the activity of any of these steps. For example:

* **Inhibition of E3 ligases:** Some proteins can bind to and inhibit E3 ligases, preventing the ubiquitination of target proteins.
* **Degradation of ubiquitin:** Enzymes can degrade ubiquitin, reducing its availability for ubiquitination.
* **Blocking proteasome activity:** Inhibitors can bind to the proteasome and prevent its function.
* **Promoting protein folding:** Chaperone proteins can help misfolded proteins to fold correctly, reducing the need for degradation.

This negative regulation is crucial for maintaining cellular homeostasis, preventing the degradation of essential proteins, and ensuring the appropriate regulation of cellular processes.'
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Proteins (3)

Compounds (99)